5-Bromo-2-chlorobenzaldehyde → (5-Bromo-2-chloro-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanol

(5-Bromo-pyridin-2-yl)-(2,4-difluoro-phenyl)-amine (3 g; 10.5 mmol) is dissolved in THF (70 ml) and cooled to −78 C. nBuLi (14.5 ml of a 1.5M solution in hexane; 23 mmol) is added dropwise and the resulting yellow suspension stirred or 20 min. 5-Bromo-2-chlorobenzaldehyde in THF (6 ml) is added at −78 C. After 5 min at −78 C, the reaction mixture is warmed to −50 C, poured on water and extracted with TBME twice. The combined organic phases are dried over Na2SO4 and evaporated to dryness. Purification via chromatography (SiO2; acetone/hexanes 6/94>12/88) yields the title compound as orange viscuous oil, (2.58 g; 58%) which is used in the next step. b) (5-Bromo-2-chloro-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone

1. temperaturecooled to −78 C
2. addition23 mmol) is added dropwise
3. waitAfter 5 min at −78 C
4. temperaturethe reaction mixture is warmed to −50 C
5. additionpoured on water
6. extractionextracted with TBME twice
7. dry with materialThe combined organic phases are dried over Na2SO4
8. customevaporated to dryness
9. customPurification via chromatography (SiO2; acetone/hexanes 6/94>12/88)

ORD-Eintrag

ord-e0baec73d29840bfbd8462f3aa5cdda8

Quelldatensatz

uspto-grants-2005_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06919336B2